Research Paper Details Advances, Obstacles In The Treatment of Kaposi’s Sarcoma
TAG’s Michael Marco and APLA’s Marty Majchrowicz debuted their joint collaboration, “The KS Project Report: Current Issues in Research and Treatment of Kaposi’s Sarcoma” at the X International Conference in Yokohama before the otherwise listless press corps. Following is the executive summary of that 85-page analysis. It is available, for a small fee, by writing to TAG.
AIDS-associated Kaposi’s sarcoma (KS) is an unusual malignancy first noted in 1981 at the start of the global HIV pandemic. The epidemiology of KS is unusual in that it is mainly confined to a subset of the HIV-infected population, gay and bisexual men, suggesting that KS may be linked to an as-yet undiscovered infectious agent or co-factor other than HIV. While the etiology of AIDS-KS remains to be determined, its pathogenesis has recently been partially explained as the result of inflammatory processes in endothelia cells leading to spindle-cell formation, neo-angiogenesis, edema, and ultimately, a multi-focal, apparently non-clonal neoplastic disease.
KS sometimes appears relatively early during HIV-associated immune dysregulation, and may be indolent in course. Later in disease, KS is more often found in visceral organs, and when found in the lungs may be fatal. Whether cutaneous or visceral, cosmetic or life-threatening, KS imposes a major burden on the quality of life of people with HIV, and may become life-threatening. Currently we lack reliable evidence about the incidence and severity of KS in all HIV-infected populations, but it appears to be becoming more common and more severe as people with HIV survive or avoid multiple opportunistic complications.
Current standard-of-care treatment for KS remains incompletely validated and disappointing. While interferon alpha has shown limited anti-KS activity in people with relatively intact immune systems and CD4 counts over 200/mm3, progressive disease in persons with more advanced immunodeficiency is only imperfectly controlled with combination cytotoxic chemotherapies such as adriamycin, bleomycin and vincristine (ABV).
Against the limited clinical utility of these approved agents must be set their toxicities, expense and inconvenience. Novel experimental approaches to the treatment of KS are now in preliminary studies, including liposomally-encapsulated anthracyclines, cytokines and their inhibitors, and several kinds of angiogenesis inhibitors. The safety, efficacy and optimal uses of these agents remain to be defined in well-controlled clinical studies.
Current opinion among AIDS oncologists, infectious disease specialists, and primary care AIDS clinicians remains divided about when to initiate anti-KS therapy, what are the optimal regimens and how best to integrate KS management into the spectrum of HIV primary care.
Currently, research on the etiology, pathogenesis, epidemiology and treatment of KS remains inadequately supported by the National Institutes of Health (NIH). KS clinical trials programs remain ill-coordinated between multiple networks separately funded by the National Cancer Institute (NCI) and the National Institute of Allergy and Infectious Disease (NIAID). We recommend a series of new scientific initiatives and programs to resolve these problems and improve our understanding of and clinical management of AIDS-associated Kaposi’s sarcoma, a disease which eventually afflicts over 30% of people with AIDS living in the United States.